Mucus is comprised of high molecular weight proteins. It is a heterogeneous mix of primarily water, electrolytes, lipids, and proteins in a gel matrix. Goblet cells and submucosal glands that are located along the tracheobronchial tree produce it. Mucus is secreted in response to irritation of the airways and is elicited by viral, bacterial, and of major import, environmental contamination, primarily small particulates and allergens.
Airway hygiene and integrity also depends on mucociliary clearance (MCC), which in turn depends upon the movement of viscoelastic mucus along the tracheobronchial tree by the beating of the ciliary appendages of airway epithelial cells. However, because mucus secretions are viscous and thick, it is difficult for the ciliary appendages to move them, and excess accumulation further burdens the mucociliary functions. Conditions that encumber MCC result in an inflammatory response to the airway and increase the risk of colonization by microorganisms, such as pathogens, which if chronic, up regulate mucus production. Encumbered MCC may thus result in a vicious cycle of inflammatory damage with the potential for future damage to both the upper and lower airway. See e.g., Cole P., Minerva Anestesiol. 2001 April; 67(4):206-9, “Pathophysiology and treatment of airway mucociliary clearance. A moving tale.” Additionally, mucociliary dyskinesia, a condition of impaired mucociliary movement in the airways, is derived from a number of similar vectors, including environmental, and likewise result in impaired mucociliary clearance times of respiratory secretions. See e.g., Pedersen M. Lung. 1990; 168 Suppl: 368-76, “Ciliary Activity and Pollution.” Of note is the role of nitric oxide in secondary ciliary dyskensia found in inflammatory disorders of the respiratory tract.
In equine mammals, for example, excessive mucus accumulation and the resulting inflammation prevalence may be present in as great as 33% of the population. Inflamed airways resulting from viral, bacterial, or environmental vectors result in excess mucus residence. Excessive mucus accumulation is a significant risk factor for poor performance in racehorses. See e.g., S. J. Holcombe, N. E. Robinson, F. J. Derksen, et. al. 50th Annual Convention of the American Association of Equine Practitioners, 2004 (www.ivis.org), 4 Dec. 2004; P1441.1204, “Trachea Mucus Is Associated With Poor racing Performance In Thoroughbred Horses.”
Furthermore, excessive mucus accumulation often manifests into Inflammatory Airway Disease (IAD). In humans, mucus accumulation also accompanies several respiratory diseases and conditions, such as acute bronchitis, chronic pulmonary disease, Bronchiectasis and Cystic Fibrosis.
Attempts at treating these airway derangements have focused on a wide range of interventions (antimicrobials, mucolytics, etc.) with limited success, particularly as it applies to the performance horse. Thus, there exists a need for more effective treatment methods for treating and preventing excess mucus accumulation and related pathology.